Liddle syndrome due to a novel mutation in the γ subunit of the epithelial sodium channel (ENaC) in family from Russia: a case report.

Autor: Kozina AA; Institute of Biomedical Chemistry, Pogodinskaya street 10 building 8, 119121, Moscow, Russia.; Pirogov Russian National Research Medical University, Ostrovitianova street 1, 117997, Moscow, Russia., Trofimova TA; Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Taldomskaya str 2, 125412, Moscow, Russia., Okuneva EG; Genotek Ltd., Nastavnicheskii pereulok 17/1, 105120, Moscow, Russia., Baryshnikova NV; Pirogov Russian National Research Medical University, Ostrovitianova street 1, 117997, Moscow, Russia.; Genotek Ltd., Nastavnicheskii pereulok 17/1, 105120, Moscow, Russia., Obuhova VA; Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Taldomskaya str 2, 125412, Moscow, Russia., Krasnenko AY; Pirogov Russian National Research Medical University, Ostrovitianova street 1, 117997, Moscow, Russia.; Genotek Ltd., Nastavnicheskii pereulok 17/1, 105120, Moscow, Russia., Tsukanov KY; Genotek Ltd., Nastavnicheskii pereulok 17/1, 105120, Moscow, Russia., Klimchuk OI; Genotek Ltd., Nastavnicheskii pereulok 17/1, 105120, Moscow, Russia., Surkova EI; Genotek Ltd., Nastavnicheskii pereulok 17/1, 105120, Moscow, Russia. esurkova@genotek.ru., Shatalov PA; Veltischev Research and Clinical Institute for Pediatrics of the Pirogov Russian National Research Medical University, Taldomskaya str 2, 125412, Moscow, Russia.; Genotek Ltd., Nastavnicheskii pereulok 17/1, 105120, Moscow, Russia., Ilinsky VV; Institute of Biomedical Chemistry, Pogodinskaya street 10 building 8, 119121, Moscow, Russia.; Pirogov Russian National Research Medical University, Ostrovitianova street 1, 117997, Moscow, Russia.; Genotek Ltd., Nastavnicheskii pereulok 17/1, 105120, Moscow, Russia.; Vavilov Institute of General Genetics, Gubkina street 3, 119333, Moscow, Russia.
Jazyk: angličtina
Zdroj: BMC nephrology [BMC Nephrol] 2019 Oct 26; Vol. 20 (1), pp. 389. Date of Electronic Publication: 2019 Oct 26.
DOI: 10.1186/s12882-019-1579-4
Abstrakt: Background: Liddle syndrome is a monogenic disease with autosomal dominant inheritance. Basic characteristics of this disease are hypertension, reduced concentration of aldosterone and renin activity, as well as increased excretion of potassium leading to low level of potassium in serum and metabolic alkalosis. The cause of Liddle syndrome is missense or frameshift mutations in SCNN1A, SCNN1B, or SCNN1G genes that encode epithelial sodium channel subunits.
Case Presentation: We describe a family with Liddle syndrome from Russia. 15-year-old proband has arterial hypertension, hypokalemia, hyporeninemia, metabolic alkalosis, but aldosterone level is within the normal range. At 12 years of age, arterial hypertension was noticed for the first time. We identified novel frameshift mutation c.1769delG (p.Gly590Alafs) in SCNN1G, which encodes the γ subunit of ENaC in vertebrates. The father and younger sister also harbor this heterozygous deletion. Treatment with amiloride of proband and his sister did not normalize the blood pressure, but normalized level of plasma renin activity.
Conclusions: Our results expand the mutational spectrum of Liddle syndrome and provide further proof that the conserved PY motif is crucial to control of ENaC activity. Genetic analysis has implications for the management of hypertension, specific treatment with amiloride and counselling in families with Liddle syndrome.
Databáze: MEDLINE
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